Lesinurad: a novel therapeutic option in the pharmacotherapy of gout

Damal Kandadai Sriram, Surendran Venkatesan, Melvin George

Abstract

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Current therapies for chronic gout include mainly allopurinol and febuxostat. Inspite of the availability of these medications for several years, a significant number of patients do not have adequate control of uric acid levels resulting in acute gout flares. Lesinurad is the most recent drug molecule approved by US FDA & EMA for the treatment of gout in patients with uncontrolled gout along with allopurinol. Lesinurad prevents reabsorption of uric acid from the renal tubules, resulting in uricosuria. The efficacy of the lesinurad was demonstrated in three randomized phase 3 controlled clinical trials where the drug was primarily evaluated in the setting of background therapy with allopurinol or febuxostat. There is a definite risk of nephrotoxicity with monotherapy and when the drug is used in patients who have inadequate renal function. The drug does appear to be relatively safe, though the inconclusive cardiovascular safety of the drug has prompted the regulatory agency to mandate post marketing trials to evaluate the safety of this molecule. Nevertheless, lesinurad does appear to have a lot of promise as a front line drug molecule in the control of hyperuricemia.

Lesinurad in Combination With a Xanthine Oxidase Inhibitor for Treatment of Hyperuricemia Associated With Gout. Briefing Document for the Arthritis Advisory Committee. Available from http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM467951.pdf.